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Background The impact of glioma location on quality of life (QOL) has not been conclusively studied, possibly due to the prohibitively high sample size that standard statistical analyses would require and the inherent heterogeneity of this disease. By using a novel algorithm, we investigated the impact of tumor location on QOL in a limited set of 53 consecutive patients. Methods The glial tumors of 53 consecutive patients were segmented and registered to a standardized atlas. The Euclidian distance between 90 brain regions and each tumor's margin was calculated and correlated to the patient's self-reported QOL as measured by the Sherbrooke Neuro-Oncology Assessment Scale questionnaire. Results QOL was not correlated to tumor volume, though a significant correlation was observed with its proximity to these areas: right supramarginal gyrus, right rolandic operculum, right superior temporal gyrus, right middle temporal gyrus, right angular gyrus, and right inferior parietal lobule. Interestingly, all identified areas are in the right hemisphere, and localized in the temporoparietal region. We postulate that the adverse relation between proximity to these areas and QOL results from disruption in visuospatial functioning. Conclusions Although the areas identified in this study are traditionally considered non-eloquent areas, tumor proximity to these regions showed more impact on QOL than any other brain regions. We postulate that this effect is mediated via an adverse impact on the visuospatial functioning.

Background Past studies have shown that pain memories are often inaccurate, a phenomenon known as mnemonic pain bias. Pain memories are thought to play an important role on how future pain is felt. Recent evidence from our laboratory suggests that individuals who exaggerate past pain display increased superior temporal gyrus (STG) and parahippocampal gyrus (PHG) activity during the encoding of experimental painful stimulations, suggesting that these brain structures play an important role in pain memories. Objective /hypothesis To determine whether a virtual lesion paradigm, targeting the STG during pain encoding, can affect long-lasting pain memories. We hypothesized that interfering with the activity of the STG (and possibly of the PHG via distant/ remote effects) would attenuate mnemonic bias. Methods Randomized double-blind study with two parallel groups. Participants received either sham (n = 21) or real (n = 21) transcranial magnetic stimulation (TMS - virtual lesion paradigm) over the STG during pain encoding (milliseconds after the administration of a painful stimuli). Pain intensity and unpleasantness were evaluated using a visual analog scale (VAS; 0 to 10) immediately after the painful event, and at recall, 2 months later. The mnemonic pain bias (calculated by subtracting the pain scores obtained at recall from the pain score obtained during encoding) was compared between the two groups for both pain intensity and unpleasantness. Results Participants in both groups did not differ in terms of age and gender (real TMS = 27 years ± 9, 43% female; sham TMS = 25 years ± 4, 49% female; p > 0.64). The mnemonic bias related to pain intensity was similar in both groups (p = 0.83). However, the mnemonic bias related to pain unpleasantness was lower in the real TMS group (p = 0.04). Conclusions Our results provide the first evidence that the STG and/or the PHG, and possibly the PHG, are causally involved in the formation of biased memories of pain unpleasantness.

Background: In the past two decades, there has been increasing evidence to suggest that trigeminal neuralgia (TN) may be linked to a dysfunction of the autonomic nervous system (ANS). The aim of the present study was to formally test this hypothesis by comparing the reactivity of the ANS to experimental pain in a population of TN patients and healthy controls. Methods: Twelve patients diagnosed with classical TN and 12 healthy controls participated in the study. Cardiac activity was assessed while participants were instructed to rest and again during a cold pressor test (CPT). Heart rate variability analyses were performed off-line to obtain parasympathetic (high-frequency) and sympathetic (low-frequency) indices. Results: At baseline, ANS measures did not differ between healthy controls and TN patients, and both groups showed a similar increase in heart rate during the CPT (all p values >0.05). However, TN patients showed a greater increase in cardiac sympathetic activity and a greater decrease in cardiac parasympathetic activity during CPT compared with healthy controls (all p values Conclusions: These results suggest that TN, like many other short-lasting, unilateral facial pain conditions, is linked to ANS alterations. Future studies are required to determine if the altered ANS response observed in TN patients is a cause or a consequence of TN pain

Background and purpose Many psychological factors are known to influence pain perception. Among them, intolerance of uncertainty (IU) may play a key modulating role in situations where uncertainty prevails, especially uncertainty regarding the timing of painful events. The objective of this study was to explore the impact of individual differences in IUon pain perception during predictable and unpredictable stimulation timings. We hypothesized that people with high IU, as opposed to those with low IU, would perceive more pain when the timing of painful stimulations cannot be predicted, as compared to when they can. Methods Twenty (20) healthy adults, aged between 18 and 35 years old, were recruited. Painful sensations were provoked using transcutaneous electrical stimulations of the right sural nerve. By measuring IU (Intolerance of Uncertainty Scale) and subjective pain (verbal numerical rating scale), it was possible to test the relationship between IU and pain perception, by simulating predictable and unpredictable painful experiences. This was done through cued shock interval (CSI) blocks, with either variable timing or fixed timings (long or short time frame). Self-administered questionnaires were also used to measure pain hypervigilance, pain catastrophizing, state anxiety, and trait anxiety. Results Pearson correlations confirmed the presence of an association (r = 0.63) between IU and the change in pain intensity provoked by unpredictable stimulation timings. Importantly, this association was significant only for stimulations provided at long CSIs, indicating that higher IU scores predicted higher pain intensity scores when stimulation timings became unpredictable, and when the cued delay was long. No association was found between pain scores and other psychological variables. Conclusions Our results show that IU moderately correlates to the change in pain intensity provoked by unpredictable stimulation timings. High IU scores were associated with a worsening of the subjective pain experience, especially during long delays in an unpredictable situation. These observations suggest that IU could be considered as a psychological variable that is able to influence pain perception in certain situations. Implications Assessing and addressing IU could be an added value in pain-related therapy, especially in chronic pain.

Sex differences in pain perception are still poorly understood, but they may be related to the way the brains of men and women respond to the affective dimensions of pain. Using a matched pain intensity paradigm, where pain intensity was kept constant across participants but pain unpleasantness was left free to vary among participants, we studied the relationship between pain unpleasantness and pain-evoked brain activity in healthy men and women separately. Experimental pain was provoked using transcutaneous electrical stimulation of the sural nerve while pain-related brain activity was measured using somatosensory-evoked brain potentials with source localization. Cardiac responses to pain were also measured using electrocardiac recordings. Results revealed that subjective pain unpleasantness was strongly associated with increased perigenual anterior cingulate cortex activity in women, whereas it was strongly associated with decreased ventromedial prefrontal cortex activity in men. Only ventromedial prefrontal cortex deactivations in men were additionally associated with increased autonomic cardiac arousal. These results suggest that in order to deal with pain's objectionable properties, men preferentially deactivate prefrontal suppression regions, leading to the mobilization of threat-control circuits, whereas women recruit well-known emotion-processing areas of the brain. Perspective This article presents neuroimaging findings demonstrating that subjective pain unpleasantness ratings are associated with different pain-evoked brain responses in men and women, which has potentially important implications regarding sex differences in the risk of developing chronic pain.

summary Background & aims: Group B streptococci (GBS) are a major cause of neonatal infection. The existence of a link between levels of vitamin D and vaginal carriage of GBS was investigated. Methods: Vitamin D level, assayed from umbilical venous blood at birth, and the status of GBS vaginal carriage during the last term of pregnancy were available from 2246 motherechild couples. Results: Levels of vitamin D in cord blood at birth was deficient ( 30 ng/ml) in 32.1%, 53.0% and 14.9% of tested subjects, respectively. Levels differed significantly depending on the season of delivery, the duration of exposure to sunlight, the skin phototype, and on vitamin D supplementation. The percentage of GBS vaginal carriage was 15.4. A negative association was observed between GBS vaginal carriage and level of vitamin D (P < 0.01 by chi-square test). No relationship was established between GBS colonisation (27 cases identified) or infection (7 cases identified) and vitamin D status. Conclusions: A correct vitamin D level was associated with a lower rate of GBS vaginal carriage during pregnancy. This calls for the monitoring of vitamin D status in pregnant women, a screen which could greatly reduce the need for intrapartum antibiotic prophylaxis.

Although aggressive tumor resection favors survival in neuro-oncology, its effects on quality of life (QOL) are largely unspecified. The objective of the present study, therefore, was to study the relationship between tumor resection and QOL.We conducted a longitudinal study among 35 patients presenting with a suspected, and later confirmed, glioblastoma multiforme tumor. Following surgery, all patients received radiation therapy with concomitant temozolomide. Tumor volumes were segmented manually, and extent of resection was calculated by comparing pre- and post-operative volumes. QOL was obtained at intake and 3 months later, using the Sherbrooke Neuro-Oncology Assessment Scale. Change in QOL was determined by computing the difference between intake and follow-up data. Confounds were controlled for by detrending change in QOL scores from the effects of age, initial tumor volume, tumor location, and baseline QOL.Results showed that larger tumors at intake provoke increased pain (mostly headaches; r = 0.41, p = 0.015) and decreased social support/acceptance of disease (r = 0.43, p = 0.009). Results also showed that compared to biopsies, craniotomies were associated with preserved well-being across nearly all domains of QOL. When extent of resection was analyzed more specifically, results confirmed that larger resections prevented the decay in functional well-being (r = 0.616, p = 0.005) and neurocognitive function (r = 0.51, p = 0.026) typically observed as time progresses. Larger resections were also independently associated with prolonged survival.Although the data were obtained from a relatively small sample of patients, results indicate that aggressive resections avert decay in QOL, and thus prolong optimized survival.

Objective Ever since the characterization of schizophrenia, clinicians have noted abnormal pain sensitivity in their patients. The published literature, however, is inconsistent concerning the nature of the change reported. The objective of this study was to characterize the pain response profile of schizophrenic patients by providing both acute and prolonged (i.e., rapidly repeating) painful stimuli to schizophrenic participants and control subjects. Participants Twelve schizophrenic subjects and eleven controls were included in the final analysis. Diagnosis was made according to Diagnostic and Statistical Manual of mental disorders-4th edition, text revision (DSM-IV-TR) criteria. Methods Intermittent, transcutaneous stimulations of the left sural nerve were administered to all participants. Painful sural nerve stimulations provoked a nociceptive flexion reflex response which was measured using an electromyographic recording of the bicep femoris muscle. Pain ratings were obtained using a 0–10 verbal numerical scale. Among schizophrenic participants, the relationship between subjective pain, reflex amplitude, and clinical features was investigated. The Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, and Subjective Scale to Investigate Cognition in Schizophrenia were used to evaluate clinical features. Results Compared with controls, schizophrenic subjects showed increased sensitivity to acute pain (i.e., lower pain thresholds; P = 0.019), but decreased subjective pain sensitization (P = 0.027). Group differences in subjective pain sensitization were not accompanied by group differences in nociceptive reflex activity (P = 0.260), suggesting supraspinal origins to the change in pain experienced by schizophrenic subjects. Moreover, positive symptoms correlated negatively with pain threshold values among schizophrenic participants (r = −0.696, P = 0.012), suggesting that distortions of thought and function relate to pain sensitivity in schizophrenic patients. Conclusion Results indicate that schizophrenic subjects present a specific experimental pain response profile, characterized by elevated sensitivity to acute pain but reduced sensitivity to prolonged pain.

Previous studies suggested that pulsed electromagnetic field (PEMF) therapy can decrease pain. To date, however, it remains difficult to determine whether the analgesic effect observed in patients are attributable to a direct effect of PEMF on pain or to an indirect effect of PEMF on inflammation and healing. In the present study, we used an experimental pain paradigm to evaluate the direct effect of PEMF on pain intensity, pain unpleasantness, and temporal summation of pain. Twenty-four healthy subjects (mean age 22 ± 2 years; 9 males) participated in the experiment. Both real and sham PEMF were administered to every participant using a randomized, double-blind, cross-over design. For each visit, PEMF was applied for 10 minutes on the right forearm using a portable device. Experimental pain was evoked before (baseline) and after PEMF with a 9 cm(2) Pelletier-type thermode, applied on the right forearm (120 s stimulation; temperature individually adjusted to produce moderate baseline pain). Pain intensity and unpleasantness were evaluated using a 0-100 numerical pain rating scale. Temporal summation was evaluated by comparing pain intensity ratings obtained at the end of tonic nociceptive stimulation (120 s) with pain intensity ratings obtained after 60 s of stimulation. When compared to baseline, there was no change in pain intensity and unpleasantness following the application of real or sham PEMF. PEMF did not affect temporal summation. The present observations suggest that PEMF does not directly influence heat pain perception in healthy individuals.

Background:The impact of malignant glioma resection on survival is still a matter of controversy. The lack of well-designed prospective studies as well as control of all factors in retrospective studies plays an important role in this debate. Amongst some of these uncontrolled factors, are the inclusion of different histological grades, the lack of objective methods to estimate the extent of resection and unspecified delays in post-operative imaging.Methods:We retrospectively reviewed 126 consecutive patients with glioblastoma, operated on by the senior authors at the Centre Hospitalier Universitaire de Sherbrooke, who met the following criteria: >18 years of age, newly diagnosed glioblastoma, pre-operative magnetic resonance imaging (MRI) within 2 weeks prior to surgery, and a post-operative MRI within 72 hours after surgery. Extent of tumour resection was calculated using pre and post-operative tumour delimitation on gadolinium-enhanced T1 MRI in a volumetric analysis.Results:Applying stringent specific inclusion criteria, 126 patients were retained in the analysis. The median overall survival was 271 days and the median extent of resection was 65%. Patients with more than 90% of tumour resection had a significantly better outcome, improving median survival from 225 to 519 days (P=0.006). Other factors that significantly improved survival were the use of radiotherapy, the number of regimens and type of chemotherapy used.Conclusion:A more aggressive approach combining maximal safe resection and use of salvage chemotherapy seems to confer a survival advantage for glioblastoma patients.

Previous human studies have shown that the analgesic effect of high-frequency TENS could not be reversed by low doses of naloxone. The aim of the present study was to reinvestigate the possible contribution of opioid receptors to high-frequency TENS analgesia by using low (0.02 mg/kg) and high (0.14 mg/kg) doses of naloxone. Naloxone (high and low doses) and saline were administered intravenously to young healthy adults using a triple-blind randomized cross-over design. For each visit, TENS (100 Hz, 60 μs) was applied for 25 min to the external surface of the left ankle. TENS intensity was adjusted to obtain strong but comfortable (innocuous) paresthesias. Experimental pain was evoked with a 1 cm(2) thermode applied on the lateral aspect of the left heel. Subjective pain scores were obtained before, during and after TENS. Because preliminary analyses showed that the order of presentation affected the pattern of results, only the first visit of every participant could be analyzed without fear of contamination from possible carry-over effects. These revealed that TENS maintained its analgesic properties following the injection of saline (p

Object Due partly to therapeutic improvements and prolonged patient survival, the field of neurooncology is gradually undergoing a philosophical shift, progressively moving toward a more functional approach to patient welfare. This shift includes, as one of its defining objectives, the promotion of elevated levels of quality of life (QOL) and quality of health (QOH) for patients of all ages. Unfortunately, an adult life-stage perspective has never been used to study the long-lasting impact of age on well-being in neurooncology patients. Methods In this study, the authors assessed and compared the QOL and QOH scores of 42 younger adults (≤ 40 years of age) and 88 older adults (> 40 years of age) presenting with a primary supratentorial tumor. Results After having controlled for biomedical and treatment-related factors, the authors discovered that older adults reported lower functional well-being and poorer neurocognitive functioning than younger adults. This age difference appeared earlier than expected (developing as early as middle age), suggesting an accelerated effect of disease on the aging process. Importantly, it was also found that the variables that predict QOL and QOH differed depending on patient age. For example, support from friends was a significant predictor of QOL for younger adults, whereas the capacity to continue enjoying life was a significant predictor for older adults. Moreover, the presence of a high-grade tumor and increased physical pain had a negative impact on the QOH of younger adults, whereas increased difficulty with concentration negatively impacted the QOH of older adults. Conclusions These age differences clearly warn against consolidating the QOL or QOH scores of younger and older adults, and instead suggest that age at diagnosis is essential when considering patient perspective, and when establishing tailored support programs.

Trigeminal neuralgia (TN) is a rare neuropathic facial pain disorder. Two forms of TN, classical TN (CTN) and atypical TN (ATN), are reported and probably have different aetiologies. The aim of the present study was to evaluate the functional integrity of the diffuse noxious inhibitory controls (DNIC) in (1) a group of patients with classical trigeminal neuralgia (CTN), (2) a group of patients with atypical trigeminal neuralgia (ATN), and (3) a group of healthy controls in order to determine if a descending pain modulation deficit could participate in the pathophysiology of TN pain. DNIC responses of 14 CTN patients, 14 ATN patients and 14 healthy controls were obtained by comparing thermode-induced facial heat pain scores before and after activating DNIC. DNIC was triggered using a standard counter-irritation paradigm (i.e., immersion of the arm in painfully cold water). General sensitivity to pain was also evaluated by measuring mechanical pain thresholds over 18 points located outside the trigeminal territory. Healthy participants and CTN patients showed a 21% and 16% reduction in thermode-induced pain following the immersion, respectively (all p-values.01), whereas ATN patients experienced no change (p=.57). ATN patients also had more tender points (mechanical pain thresholds4.0kg) than CTN and healthy controls (all p-values.05). Taken together, these results suggest that the underlying physiopathology differs between CTN and ATN and that a deficit in descending inhibition may further contribute to the pain experienced by patients with ATN.

Three infants presenting with severe cases of infantile botulism, occurring at 17, 30, and 180 days of life, respectively, are described in this report. All three infants presented with areflexive flaccid coma or apnoeas requiring prolonged ventilation. In serum, type B botulinum neurotoxin (BoNT/B) was detected in two cases and BoNT/A in the third case, confirming the diagnosis of infantile botulism. Despite constant nursing and monitoring, the recovery of motility was progressive, but finally complete. Dysautonomia, measured by recording heart rate variability (HRV), persisted beyond observable physical recovery. Dysautonomia was assessed using a time-domain analysis of the continuous electrocardiogram response (via non-invasive weekly 24 h Holters), which included sympathetic (SDNN) and parasympathetic indices (RMS-SD, pNN50). In all three of our patients, we observed an initial hypotonic period and a major decrease in all HRV indices. Despite observable recovery shortly after extubation, HRV time domain indices remained altered for many weeks. Because of the close monitoring afforded by hospitalization, this change in autonomic function was not accompanied by syncope, complications arising from ventricular arrhythmia, or sudden death. Our observations have important clinical implications since they emphasize the importance of pursuing cardiopulmonary monitoring following apparent functional recovery from the BoNTs.

In healthy adults, expectations can modulate the activity of inhibitory bulbo-spinal projections, and can even block the analgesic properties of counter-irritation - a phenomenon that triggers descending inhibition. Since descending inhibition is known to be deficient in fibromyalgia (FM) patients, we tested the possibility that expectancy-mediated analgesia would improve, or even kick-start, the deficient inhibitory responses of FM patients. By measuring subjective pain ratings, spinal withdrawal reflexes, and somatosensory evoked potentials (SEP), it was possible to test whether or not expectancy-mediated analgesia involved descending inhibition in FM patients. Here, we show that expectations of analgesia radically change the subjective experience of pain, but do not eliminate evidence of spinal hyperexcitability in FM patients. We found that expectations of analgesia reduce subjective pain ratings and decrease SEP amplitudes, confirming that expectations influence thalamocortical processes. However, even when analgesia was experienced, the spinal activity of FM patients was abnormal, showing heightened reflex responses. This demonstrates that, unlike healthy subjects, the modulation of pain by expectations in FM fails to influence spinal activity. These results indicate that FMs are capable of expectancy-induced analgesia but that, for them, this form of analgesia does not depend on the recruitment of descending inhibitory projections.

On pathophysiologic grounds, fibromyalgia (FM) is characterized by a deficit in diffuse noxious inhibitory controls (DNIC), but the role of depressive symptoms on these mechanisms has not been investigated. We hypothesized that the deficit in pain inhibition would be more pronounced in FM patients with depressive symptoms (FM+D), relative to patients without such symptoms (FM-D).Fifty-two women diagnosed with FM (American College of Rheumatology criteria) and 10 healthy women participated in this study. Thermal stimuli were used to measure pain thresholds and DNIC efficacy (spatial summation paradigm). Clinical pain was measured using visual analog scales.We found that the amplitude of DNIC was smaller in FM+D patients, relative to the FM-D group; and that daily pain (unpleasantness) was higher in the FM+D group, relative to FM-D patients.We found that FM+D patients have a more pronounced deficit in pain inhibition as well increased clinical pain. As such, these results show the usefulness of combining psychologic factors and psychophysical measures to identify subgroups of FM patients. These results may have implications for future treatment of FM patients with and without comorbid depressive symptoms.

Objectives Previous studies have shown a reduction of diffuse noxious inhibitory controls (DNICs) in elderly adults compared with younger adults. Unfortunately, little is known regarding the developmental course of DNIC deficits and so it is still unclear whether middle-aged adults also show a DNIC deficit. The aims of the present study were to better characterize the developmental time course of the change in DNIC response by adding a middle-aged group. The role of expectations was also investigated. Methods The pain thresholds (PTs) of 20 young, 20 middle-aged, and 20 healthy elderly volunteers were assessed before and during a cold pressor task (water at 7 degrees C). Acute nociceptive stimuli were administered using a thermode and consisted of a range of painless and painful heat pulses. Results Analyses showed that thermal PTs increase by middle age but that the DNIC-induced increase in PT dampens progressively with advancing age. DNIC response was negatively correlated with advancing age, however, expectations regarding DNIC efficacy did not vary with age. This suggests that age-related changes in the size of the DNIC response are not best explained by an age-related change in expectation. Discussion The findings tell us that changes in pain perception and endogenous pain modulation arrive earlier than previously suggested. Studies on aging and pain should include a middle-aged group when comparing pain measures across the adult lifespan.

Objectives Recent studies demonstrate that empathy-evoked brain responses include the activation of brainstem structures responsible for triggering descending pain inhibition. Unfortunately, direct evidence linking empathy for pain and descending inhibitory controls (conditioned pain modulation) is lacking. This study, therefore, aimed to determine if the observation of ourselves or a loved-one in pain could activate descending pain inhibition without exposure to a noxious stimulation; which is otherwise required. Methods Descending pain inhibition was triggered by immersing the right arm of participants (15 heterosexual couples; mean age±SE: 28.89±2.14) in a bath of cold water. The effects of empathy on descending pain inhibition were observed by immersing the right arm of participants in a bath of lukewarm water while having them watch a video of either themselves or their spouse during a previous nociceptive immersion. Immersion of the arm in a bath of lukewarm water without empathic (video) observation was also included as a control condition. Results A strong inhibitory response activated by the mere observation of the video of themselves or their spouse in pain without a nociceptive conditioning stimulus. Associative statistics also showed that strong pain catastrophizing responses while watching the video resulted in stronger pain inhibition. Moreover, high levels of empathy were associated with stronger pain inhibition, but only for women. Discussion This study showed that observing someone in pain triggers descending pain inhibition. Results also demonstrate how empathy and gender are affecting pain modulation mechanisms.

Background: Pain perception ratings in irritable bowel syndrome(IBS) patients suggest that they present either hypoalgesia orhyperalgesia. However, little is known about the physiologicresponses these patients present to a somatic painful stimulus.Goals: The main goal of this project was to study autonomicnervous system responses and the cardiac response to experi-mental pain in IBS patients.Study: This was addressed by exposing 27 women, 14 IBS, and13 healthy controls (HCs), to a cold water (71C) immersion testof the forefoot for 2 minutes. Pain perception, galvanic skinresponses (GSR), and heart rate (HR) were monitored duringand after the immersion.Results: For comparable pain perception, a significant groupdifference (P

A deficit of endogenous pain inhibitory systems has been suggested to contribute to some chronic pain conditions, one of them being fibromyalgia. The aim of the investigation was to test whether endogenous pain inhibitory systems were activated by a spatial summation procedure in 30 fibromyalgia, 30 chronic low back pain, and 30 healthy volunteers who participated in a cross-over trial (two sessions). Each session consisted of visual analog scale ratings of pain during the immersion of different surfaces of the arm in circulating noxious cold (12 degrees C) water. The arm was arbitrarily divided into eight segments from the fingertips to the shoulder. One session was ascending (from the fingertips to the shoulder) and the other was descending (from the shoulder to the fingertips); they included eight consecutive 2-min immersions separated by 5-min resting periods. For healthy and low back pain subjects, pain was perceived differently during the ascending and descending sessions (P=0.0001). The descending session resulted in lower pain intensity and unpleasantness. This lowering of the perception curve seems to be due to a full recruitment of inhibitory systems at the beginning of the descending session as opposed to a gradual recruitment during the ascending session. For fibromyalgia subjects, no significant differences were found between the increasing and decreasing sessions (P>0.05). These data support a deficit of endogenous pain inhibitory systems in fibromyalgia but not in chronic low back pain. The treatments proposed to fibromyalgia patients should aim at stimulating the activity of those endogenous systems.

Several studies have suggested that glucose hypometabolism may be present in specific brain regions in cognitively normal older adults and could contribute to the risk of subsequent cognitive decline. However, certain methodological shortcomings, including a lack of partial volume effect (PVE) correction or insufficient cognitive testing, confound the interpretation of most studies on this topic. We combined [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging to quantify cerebral metabolic rate of glucose (CMRg) as well as cortical volume and thickness in 43 anatomically defined brain regions from a group of cognitively normal younger (25 ± 3 yr old; n = 25) and older adults (71 ± 9 yr old; n = 31). After correcting for PVE, we observed 11–17% lower CMRg in three specific brain regions of the older group: the superior frontal cortex, the caudal middle frontal cortex, and the caudate ( P ≤ 0.01 false discovery rate-corrected). In the older group, cortical volumes and cortical thickness were 13–33 and 7–18% lower, respectively, in multiple brain regions ( P ≤ 0.01 FDR correction). There were no differences in CMRg between individuals who were or were not prescribed antihypertensive medication. There were no significant correlations between CMRg and cognitive performance or metabolic parameters measured in fasting plasma. We conclude that highly localized glucose hypometabolism and widespread cortical thinning and atrophy can be present in older adults who are cognitively normal, as assessed using age-normed neuropsychological testing measures.

Fibromyalgia (FM) is a chronic widespread pain condition of unknown origin. Reduced endogenous pain inhibition could be related to high pain sensitivity in FM. Associations between conditioned pain modulation (CPM) and cardiovascular responses to pain have been observed in healthy subjects (HS). Because reduced cardiovascular reactivity to various stressors has been reported in FM patients, we investigated relationships between CPM and cardiovascular response to the cold pressor test (CPT) in 22 FM patients and 25 HS. CPM was evaluated by comparing pain intensity produced by a 120-second heat test stimulus (HTS) before and after a CPT (2 minutes, 12°C). The CPT, used to activate CPM, produced greater pain intensity in FM patients. Patients with FM had higher heart rates than HS at baseline and during CPT. Higher heart rate was related with higher pain intensity during the CPT. Blood pressure increments during CPT were weaker in the FM group. CPM was less effective in FM patients than in HS. Importantly, systolic blood pressure responses during CPT were positively related to CPM effectiveness, suggesting that reduced blood pressure response during the conditioning stimulus could be involved in CPM dysfunction in the FM group. Higher heart rate could be implicated in the greater sensitivity to cold pain in FM. Patients with FM have reduced blood pressure response to a painful CPT. Reduced cardiovascular reactivity to pain could have important involvement in diminished endogenous pain inhibition efficacy and FM pathophysiology.

Background: Because glioblastoma is currently incurable, the goal of therapy is the optimization of the patient’s quality of life (QOL). Tumor location is critical in screening surgical candidates, yet the impact of tumor location on QOL has never been demonstrated. By using a novel computer-driven algorithm, we set out to investigate the impact of tumor location on QOL. Methods: The tumors of fourty consecutive glioblastoma patients were segmented and the Euclidian distance between 90 brain regions and each tumor’s margin was calculated and correlated to the patients’ self-reported QOL as measured by the SNAS questionnaire. Results: QOL was statistically associated with proximity to three areas: the right para-hypocampal gyrus, the right posterior cingulate cortex and the right postcentral gyrus. We postulate that the adverse relation between proximity to these areas and QOL results from disruption in large-scale networks involved in high-order functions such as visuospatial memory. While harder to detect with a bedside clinical examination, such deficits are likely more impactful on QOL than those related to the motor cortex or Broca’s area. Conclusions: Tumor proximity to right parietooccipital region are associated with decreased QOL. This should be considered in the management strategies of glioma patients.

Placebo effects are well-known phenomena in medicine and biology. In fact, placebos are used as control conditions in randomized cross-over clinical trials to validate new treatments. Only recently, however, has it become apparent that the conditioning and/or expectation effects provided by the experience of placebos can influence the results of clinical trials. It seems that combining shams and sequences has prejudiced the conclusions provided by cross-over designs. Frighteningly, this bias is always in the same direction, namely to increase the risk of rejecting potentially valid treatments. New models for clinical trials should be encouraged if we wish to market new and truly valid treatments.

INTRODUCTION: Glioblastoma is the most frequent primary brain tumor. Because it is currently incurable, the goal of therapy is the optimization of the patient's quality of life (QOL). While maximal surgical resection has been shown to improve survival and QOL, not all tumors can be safely resected. Tumor location is critical in screening surgical candidates, yet the impact of tumor location on QOL has never been convincingly demonstrated, possibly due to the prohibitively high sample size that standard statistical analyses would require. By using a novel computer-driven algorithm, we set out to investigate the impact of tumor location on QOL. METHODS: The tumors of fourty consecutive glioblastoma patients were segmented and registered to a Talairach-space standard brain image. The Euclidian distance between 90 brain regions and each tumor's margin was calculated and correlated to the patients' self-reported QOL as measured by the SNAS questionnaire. Multiple linear regression analyses were performed between QOL, tumor location and clinical parameters. RESULTS: QOL was statistically associated with proximity to three areas: the right para-hypocampal gyrus, the right posterior cingulate cortex and the right postcentral gyrus. We postulate that the adverse relation between proximity to these areas and QOL results from disruption in large-scale networks involved in high-order functions such as visuospatial memory. While harder to detect with a bedside clinical examination, such deficits are likely more impactful on QOL than those related to the motor cortex or Broca's area. CONCLUSION: Tumor proximity to the right para-hypocampal gyrus, the right posterior cingulate cortex and the right postcentral gyrus are associated with decreased QOL, probably via an impact in visuospatial functionning. While traditionally considered non-eloquent, these affected areas have more impact on QOL than any other brain region and this should be considered in the management strategies of glioma patients.

Although most people who suffer from headache do not present with an underlying mass lesion, a large number of patients with brain tumors do complain of headache (as many as 60% in our institution). The problem for clinicians is that the tumor-headache association is not universal, as evidenced by anecdotal reports of patients with large tumors, elevated intracranial pressure but a complete absence of headache. In this chapter, we examine over 80 years of research on brain tumor headaches, delineating the link between tumor location, laterality, growth-rate, and pain. Most importantly, we position our review within the context of current aetiological theories and propose new models involving the peripheral and central sensitization of nociresponsive neurons. A brief examination of headaches as a result of surgery and adjuvant chemo-radiation therapy is also provided.

The last few decades have seen an increase in the amount of research dedicated to the quality of life (QOL) of cancer survivors, especially for breast and lung cancers. Unfortunately, relatively little attention has been paid to the QOL of neuro-oncology patients. Moreover, reports on the QOL of brain cancer patients are often qualitative and/or converge on a single dimension of well-being. Future QOL studies will have to focus on multiple dimensions of QOL, establishing prospective evaluations of baseline and serial parameters. Research objectives should also include the concomitant exploration of radiological, histopathological, and patient-related factors as potential predictors of QOL. Comprehensive models are particularly useful because they can help account for the reciprocal connections often observed between baseline variables, and because they promise to shed light on some of the contradictory results observed in the field, such as the presumed long-term benefits of resection. Empirical QOL data obtained within a biopsychosocial framework may guide the development of new treatment avenues and may help promote the application of focused, patient-centered support programs.

Although most people who have headache pain do not present with an underlying mass lesion, a large number of patients with brain tumors do report headache (as many as 60% in our institution). The problem for clinicians is that the tumor-headache association is not universal, as evidenced by anecdotal reports of patients with large tumors and increased intracranial pressure, but a complete absence of headache pain. In this review, we examine more than 80 years of research on brain tumor headaches, delineating the link between tumor location, laterality, growth rate, and pain. Most importantly, we position our review within the context of current etiological theories and propose new models involving the peripheral and central sensitization of nociresponsive neurons. This review will help clinicians understand why debulking surgery sometimes fails to alleviate neoplastic headache pain in select patients. A brief examination of headaches as a result of surgery and adjuvant chemoradiation therapy is also provided. Headaches can be an early indicator of central nervous system tumors. However, headaches are present in a wide variety of other condition, and are sometimes (surprisingly) absent in patients with primary neoplasms or metastatic tumors. This observation complicates the possibility of linking headaches to brain tumors. Nevertheless, some generalizations concerning brain tumor headaches can be drawn. The following sections review these generalizations, presenting caveats where appropriate. Lingering questions in the field are also addressed and presented together with promising future research avenues.

Background Apparent life-threatening events (ALTE) and/or prolonged apnoea have been well-documented during respiratory syncytial virus (RSV) infection in infants less than 2 months of age but fundamental mechanisms remain unclear. The possibility of a central origin for the development of severe cardiac and respiratory events encouraged us, to explore the autonomic nervous system (ANS) profile of infected infants, since ANS activity may contribute to the constellation of symptoms observed during severe forms of RSV bronchiolitis. Methods Eight infants (2 preterm and 6 full-term) less than 2 months of age and presenting with severe and apnoeic forms of RSV infection were evaluated using non-invasive electrophysiological monitoring obtained simultaneously for approximately 2 consecutive hours, including a quiet sleep period. Eight control subjects, paired for gestational and postnatal age, were also evaluated. ANS status was monitored using electrocardiogram recordings and quantified through a frequency-domain analysis of heart rate variability (HRV). This included sympathetic (VLF and LF) and parasympathetic (HF) indices as well as a measure of baroreflex sensitivity (BRS) obtained using non-invasive continuous arterial pressure. Results Regardless of gestational and postnatal age, heart rate variability components (Ptot, VLF, LF, and HF) and baroreflex components (α LF, α HF and sBR) were found to be significantly lower in the RSV-infected group than in the control group ( p Conclusion RSV infection in neonates is associated with profound central autonomic dysfunction. The potentially fatal consequence stresses the importance of maintaining prolonged cardiopulmonary monitoring.

Objective. Slow deep breathing has been proposed as an effective method to decrease pain. However, experimental studies conducted to validate this claim have not been carried out. Design. We measured thermal pain threshold and tolerance scores from 20 healthy adults during five different conditions, namely, during natural breathing (baseline), slow deep breathing (6 breaths/minute), rapid breathing (16 breaths/minute), distraction (video game), and heart rate (HR) biofeedback. We measured respiration (rate and depth) and HR variability from the electrocardiogram (ECG) output and analyzed the effects of respiration on pain and HR variability using time and frequency domain measures of the ECG. Results. Compared with baseline, thermal pain threshold was significantly higher during slow deep breathing (P = 0.002), HR biofeedback (P < 0.001), and distraction (P = 0.006), whereas thermal pain tolerance was significantly higher during slow deep breathing (P = 0.003) and HR biofeedback (P < 0.001). Compared with baseline, only slow deep breathing and HR biofeedback conditions had an effect on cardiac activity. These conditions increased the amplitude of vagal cardiac markers (peak-to-valley, P < 0.001) as well as low frequency power (P < 0.001). Conclusion. Slow deep breathing and HR biofeedback had analgesic effects and increased vagal cardiac activity. Distraction also produced analgesia; however, these effects were not accompanied by concomitant changes in cardiac activity. This suggests that the neurobiology underlying respiratory-induced analgesia and distraction are different. Clinical implications are discussed, as are the possible cardiorespiratory processes responsible for mediating breathing-induced analgesia.

In this study, we explored the analgesic and antihyperalgesic properties of a synthetic cannabinoid (nabilone) on experimental heat pain in men and women, as well as its effects on descending pain inhibitory systems.A double-blind, placebo controlled, crossover study of nabilone single doses of 0.5 and 1 mg was conducted. Excitatory systems were elicited using a temporal summation test (tonic heat pain evoked by a Peltier thermode) administered before and after activation of descending inhibitory control (triggered using a counter-irritation procedure). These tests were given before and after drug treatment. Primary outcome measures included average heat pain, temporal summation of heat pain, and drug-induced changes in the strength of descending analgesia. Possible adverse reactions were monitored throughout treatment. Seven men (mean age = 22.5 years, SD = +/- 1.5) and 10 women (mean age = 23.2 years, SD = +/- 2.8) completed this study.Nabilone (1 mg and 0.5 mg) did not reduce the global pain intensity experienced during tonic heat pain (all values of p0.18). It also failed to potentiate the strength of descending inhibitory responses (all values of p43). Nevertheless, at the highest dose (1 mg), and only for women, nabilone significantly (p = 0.003) dampened the temporal summation experienced during the last portion of the tonic heat pulse test (i.e., the period of time during which temporal summation is greatest). This antihyperalgesic effect was not observed for men (at either 0.5 mg or 1 mg dose), suggesting that the antihyperalgesic properties of cannabinoids are greater for women than for men. Adverse reactions encountered were generally mild and did not provoke the cessation of testing.Nabilone failed to produce analgesic effects and it did not interact with descending pain inhibitory systems. However, we found that a single 1 mg dose of nabilone reduced temporal summation for women but not men. Although a titration regime and a larger sample of subjects might have provided more robust effects, these preliminary results suggest that nabilone appears effective at relieving hyperalgesic responses in women. Possible neurobiological mechanisms and clinical implications are further discussed.

populations, and delivery volumes in Ohio. Local data abstractors in the initial 39 Week Project were replaced by birth certificate personnel at each site who were educated by Ohio Vital Statistics staff and supported by quality improvement experts. Ohio Birth Certificate data were collected and reported promptly. Rates of scheduled inductions of labor that lacked a documented medical indication were reported in monthly QI webinars. Local teams used IHI techniques to promote compliance with ACOG practice guidelines. RESULTS: Rates of scheduled inductions of labor 39 weeks without a medical indication in the 15 pilot sites decreased while the original OPQC project was ongoing, and declined further when Ohio began reporting hospital rates on a public website. Rates have continued to decline in pilot project sites since project inception (see graph), and accuracy of birth certificate information has improved. CONCLUSION: Collaboration by clinical, administrative, and Ohio Vital Statistics staff to improve the accuracy of birth certificate data has been accompanied by a decline in scheduled births 39 weeks gestation in medium sized maternity units.